Medical Scientists To Begin Clinical Trials Of Promising Cancer Therapy

In a study so far being done only at the UNC-CH School of Medicine, the researchers will administer increasing doses of a compound known as PS341 to between 20 and 30 cancer patients to determine the highest doses they can receive without developing side effects.

Earlier work suggests that the compound will be safe and that it might boost success in treating people with stubborn cases of such blood-borne malignancies as leukemia, myeloma and lymphoma, according to Dr. Robert Z. Orlowski, assistant professor of medicine.

"Everybody here is pretty excited about this compound because it's being used experimentally at a few other universities for solid tumors," said Orlowski, a member of the Lineberger Comprehensive Cancer Center. "Although it is too early to tell how beneficial it has been in shrinking solid tumors, clinicians have observed few side effects. Our experimental data suggest it could be useful in treating non-solid tumors, and that's why we're doing this work."

Other physicians participating in the clinical trial include Drs. Tom Shea, head of the transplant program, and Beverly Mitchell, chief of hematology/oncology and head of the experimental therapeutics program.

"When talking about cancer treatments, you never want to make predictions that are too positive and lead people to be disappointed later on," Orlowski said. "However, the good thing about compounds like this is that they act in a completely different manner from all of the other available drugs. For that reason, they have the potential to help even in patients who have not benefited by currently available chemotherapy.

"Based on our laboratory work, another advantage is that cancer cells appear to be more sensitive to these compounds than normal cells are," he said. "That implies we might be able to kill cancer cells while not having much of a negative effect on normal cells."

PS341 is a protease inhibitor somewhat different from ingredients forming part of the three-drug "cocktails" used with increasing success to treat AIDS patients. A protease is an enzyme whose chief purpose is to digest - or cut up into smaller components -- other proteins so that they can be used inside cells. An inhibitor prevents the enzyme from doing its job and triggers programmed cell death known as apoptosis.

The goal in chemotherapy is to kill as many cancer cells as possible while sparing as many normal cells as possible, the physician said.

Mice in which human lymphoma tumors were grown fared significantly better when given protease inhibitors like PS341 than did mice treated with control compounds, Orlowski said. In experiments involving lymphoma cells growing in laboratory glassware, he and colleagues also found that combining the new chemicals with current cancer chemotherapy killed more cells than the total number killed by both the new and the old compounds when administered separately.

Proscript of Cambridge, Mass., makes PS341 and related compounds.

While much progress has been made in the past two decades in treating cancers like lymphoma, for example, a lot more needs to be done, Orlowski said. Currently, about half those who go into remission from advanced lymphoma will suffer a recurrence, and only about 30 percent to 40 percent of people with advanced, aggressive lymphomas can be cured.

"Clearly we need some additional chemotherapeutic agents in our armamentarium, and we hope this will benefit patients," he said.

For more information, patients with non-solid malignancies can call Stephanie Stahl at 919-966-4432 or Orlowski at 919-966-9762. Those accepted into the study will be treated initially twice a week at UNC-CH's General Clinical Research Center as inpatients, Orlowski said. If they do well, they will continue treatment as outpatients.